Time-series transcriptional profiling yields new perspectives on susceptibility to murine osteoarthritis.

Chronological age is a powerful epidemiologic risk factor for osteoarthritis (OA), a multifactorial disease that is characterized by articular cartilage (AC) degradation. It is unclear from a molecular perspective how aging interacts with OA to produce this risk to AC integrity. To address this key question, we used in vivo time-course analysis of OA development and murine interstrain variability in natural susceptibility to OA to examine changes in non-OA-prone CBA mice versus OA-prone STR/Ort mice, which develop disease that bears significant histologic resemblance to human OA. Through global transcriptome profiling, we attempted to discover the molecular signature linked with both OA vulnerability and progression. Affymetrix Mouse Gene 1.0 ST Array profiles were generated from AC samples derived from CBA and STR/Ort mice at 3 different ages, corresponding to the stages prior to, at, and late after the natural onset of OA in the STR/Ort mice. We found that the OA in STR/Ort mice exhibited a molecular phenotype resembling human OA, and we pinpointed a central role of NF-κB signaling and the emergence of an immune-related signature in OA cartilage over time. We discovered that, strikingly, young healthy AC has a highly expressed skeletal muscle gene expression program, which is switched off during maturation, but is intriguingly retained in AC during OA development in STR/Ort mice. This study is the first to show that AC chondrocytes share a high-abundance gene-expression program with skeletal muscle. We show that failure to switch this program off, as well as the restoration of this program, is associated with inappropriate expression of NF-κB signaling pathways, skeletal muscle-related genes, and induction and/or progression of OA. Copyright © 2012 by the American College of Rheumatology

Committing to ecological restoration: Efforts around the globe need legal and policy clarification

At the September 2014 United Nations Climate Summit, governments rallied around an international agreement—the New York Declaration on Forests—that underscored restoration of degraded ecosystems as an auspicious solution to climate change. Ethiopia committed to restore more than one-sixth of its land. Uganda, the Democratic Republic of Congo, Guatemala, and Colombia pledged to restore huge areas within their borders. In total, parties committed to restore a staggering 350 million hectares by 2030.Fil: Suding, Kathering. State University Of Colorado-boulder; Estados UnidosFil: Higgs, Eric. University Of Victoria; CanadáFil: Palmer, Margaret. University of Maryland; Estados UnidosFil: Callicott, J. Baird. University Of North Texas; Estados UnidosFil: Anderson, Christopher Brian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; ArgentinaFil: Baker, Matthew. University Of Maryland; Estados UnidosFil: Gutrich, John J.. Southern Oregon University; Estados UnidosFil: Hondula, Kelly L.. University of Maryland; Estados UnidosFil: Lafevor, Matthew C.. University of Maryland; Estados UnidosFil: Larson, Brendon M. H.. University Of Waterloo; CanadáFil: Randall, Alan. Ohio State University; Estados Unidos. University Of Sidney; AustraliaFil: Ruhl, J. B.. Vanderbilt University; Estados UnidosFil: Schwartz, Katrina Z. S.. Woodrow Wilson International Center for Scholars; Estados Unido

Design of a vehicle based system to prevent ozone loss

Reduced quantities of ozone in the atmosphere allow greater levels of ultraviolet light (UV) radiation to reach the earth's surface. This is known to cause skin cancer and mutations. Chlorine liberated from Chlorofluorocarbons (CFC's) and natural sources initiate the destruction of stratospheric ozone through a free radical chain reaction. The project goals are to understand the processes which contribute to stratospheric ozone loss, examine ways to prevent ozone loss, and design a vehicle-based system to carry out the prevention scheme. The 1992/1993 design objectives were to accomplish the first two goals and define the requirements for an implementation vehicle to be designed in detail starting next year. Many different ozone intervention schemes have been proposed though few have been researched and none have been tested. A scheme proposed by R.J. Cicerone, Scott Elliot and R.P.Turco late in 1991 was selected because of its research support and economic feasibility. This scheme uses hydrocarbon injected into the Antarctic ozone hole to form stable compounds with free chlorine, thus reducing ozone depletion. Because most polar ozone depletion takes place during a 3-4 week period each year, the hydrocarbon must be injected during this time window. A study of the hydrocarbon injection requirements determined that 100 aircraft traveling Mach 2.4 at a maximum altitude of 66,000 ft. would provide the most economic approach to preventing ozone loss. Each aircraft would require an 8,000 nm. range and be able to carry 35,000 lbs. of propane. The propane would be stored in a three-tank high pressure system. Missions would be based from airport regions located in South America and Australia. To best provide the requirements of mission analysis, an aircraft with L/D(sub cruise) = 10.5, SFC = 0.65 (the faculty advisor suggested that this number is too low) and a 250,000 lb TOGW was selected as a baseline. Modularity and multi-role functionality were selected to be key design features. Modularity provides ease of turnaround for the down-time critical mission. Multi-role functionality allows the aircraft to be used beyond its design mission, perhaps as an High Speed Civil Transport (HSCT) or for high altitude research

Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties

Effects of Multi-ingredient Pre-workout Supplements on Repetitions-in-Reserve and Subjective Measures of Energy, Fatigue, and Focus during Lower-Body Resistance Exercise

Approximately 50% of the U.S. population regularly consumes dietary supplements to enhance their health and well-being. One popular category of dietary supplements is called “pre-workout” supplements, which claims to increase subjective feelings of energy and exercise performance. PURPOSE: The purpose of the study was to examine whether two commercially available pre-workout supplements could beneficially modify resistance exercise-specific perceived exertion and subjective measures of energy, focus, and fatigue during an acute bout of lower-body resistance exercise. METHODS: This was a counterbalanced, double blind, placebo-controlled trial. Resistance-trained (i.e. 2+ hours per week of weight training over the past 6 months) females and males who regularly consumed caffeine (100+ mg/d) were recruited for participation. Each subject completed 3 sessions in a counterbalanced order: placebo (P), non-caffeinated pre-workout (NC; Carbon Prep), and caffeinated pre-workout (C; Jym Supplement Science Pre-Jym). At each session, identical testing was conducted using an isokinetic squat machine. One initial maximum test of 3 repetitions was completed, followed by 5 sets of 6 repetitions using 80% of the maximal force measured during the initial set of 3 repetitions. Within a 2-minute rest between each set, subjective measurements of difficulty were obtained (i.e. estimated repetitions in reserve [RIR] and 10-cm visual analog scales [VAS] for energy, focus, and fatigue). RIR ratings were converted to resistance exercise-specific ratings of perceived exertion (RPE). VAS data was analyzed using two-way repeated measures ANOVA and RIR/RPE data was analyzed for males and females separately using two-way repeated measures ANOVA. RESULTS: Twenty-one participants completed the study (12 F, 9 M). Subjective measures of energy were acutely increased by ingestion of each supplement, including placebo, but decreased as the workout progressed (time main effect; p \u3c .001). Fatigue progressively increased throughout the exercise session (time main effect; p \u3c .001). Fatigue was higher during the NC condition than the C and P conditions (supplement main effect; p = .019). A significant supplement*time interaction was present for RPE in females, but not in males. In females, the caffeinated and non-caffeinated pre-workout supplements delayed the increase in RPE as compared to placebo. CONCLUSION: The studied commercially available pre-workout supplements may beneficially delay the increase in RPE observed during acute lower-body resistance exercise in trained females. However, the results of subjective measurements should be interpreted in the context of the corresponding exercise performance

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

BACKGROUND: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment. DESIGN: We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI. RESULTS: The number of glomeruli annotated was consistently higher than those reported (p CONCLUSIONS: Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies

In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment

Projecting global mean sea-level change using CMIP6 models

The effective climate sensitivity (EffCS) of models in the Coupled Model Intercomparison Project 6 (CMIP6) has increased relative to CMIP5. We explore the implications of this for global mean sea‐level (GMSL) change projections in 2100 for three emissions scenarios. CMIP6 projections of global surface air temperature are substantially higher than in CMIP5, but projections of global mean thermal expansion are not. Using these projections as input to construct projections of GMSL change with IPCC AR5 methods, the 95th percentile of GMSL change at 2100 only increases by 3‐7 cm. Projected rates of GMSL rise around 2100 increase more strongly, though, implying more pronounced differences beyond 2100 and greater committed sea‐level rise. Inter‐model differences in GMSL projections indicate that EffCS‐based model selection may substantially alter the ensemble projections. GMSL change in 2100 is accurately predicted by time‐integrated temperature change, and thus requires reducing emissions early to be mitigated

Hyperfine Spectroscopy of Isotopically Engineered Group-IV Color Centers in Diamond

A quantum register coupled to a spin-photon interface is a key component in quantum communication and information processing. Group-IV color centers in diamond (SiV, GeV, and SnV) are promising candidates for this application, comprising an electronic spin with optical transitions coupled to a nuclear spin as the quantum register. However, the creation of a quantum register for these color centers with deterministic and strong coupling to the spin-photon interface remains challenging. Here, we make first-principles predictions of the hyperfine parameters of the group-IV color centers, which we verify experimentally with a comprehensive comparison between the spectra of spin active and spin neutral intrinsic dopant nuclei in single GeV and SnV emitters. In line with the theoretical predictions, detailed spectroscopy on large sample sizes reveals that hyperfine coupling causes a splitting of the optical transition of SnV an order of magnitude larger than the optical linewidth and provides a magnetic-field insensitive transition. This strong coupling provides access to a new regime for quantum registers in diamond color centers, opening avenues for novel spin-photon entanglement and quantum sensing schemes for these well-studied emitters